Humanized anti-IL-1β antibodies

Abstract

The present invention encompasses isolated antibodies, or antigen-binding portions thereof, that specifically bind mature human IL-1 Beta. These antibodies, or antigen-binding portions thereof, generally exhibit high binding affinities (low k oo ff values), reduced deamidation compared to the native antibody, and can be used to treat various diseases such as rheumatoid arthritis, osteoarthritis, or neuroinflammation.

1. An antibody, or an antigen-binding portion thereof, that specifically binds human IL-1β, comprising a light chain variable region and a heavy chain variable region selected from the group consisting of:
 (a) a light chain variable region encoded by the polynucleotide sequence of SEQ ID NO:60 and a heavy chain variable region encoded by the polynucleotide sequence of SEQ ID NO:55; 
 (b) a light chain variable region encoded by the polynucleotide sequence of SEQ ID NO:61 and a heavy chain variable region encoded by the polynucleotide sequence of SEQ ID NO:56; 
 (c) a light chain variable region encoded by the polynucleotide sequence of SEQ ID NO:62 and a heavy chain variable region encoded by the polynucleotide sequence of SEQ ID NO:57; 
 (d) a light chain variable region encoded by the polynucleotide sequence of SEQ ID NO:63 and a heavy chain variable region encoded by the polynucleotide sequence of SEQ ID NO:58; and, 
 (e) a light chain variable region encoded by the polynucleotide sequence of SEQ ID NO:64 and a heavy chain variable region encoded by the polynucleotide sequence of SEQ ID NO:59. 
 
     
     
       2. An antibody, or an antigen-binding portion thereof, that specifically binds human IL-1β, comprising a light chain and a heavy chain wherein the amino acid sequences of the light and heavy chains are selected from the group consisting of:
 (a) a light chain of SEQ ID NO:46 and a heavy chain of SEQ ID NO: 45; 
 (b) a light chain of SEQ ID NO:48 and a heavy chain of SEQ ID NO:47; 
 (c) a light chain of SEQ ID NO:48 and a heavy chain of SEQ ID NO:68; 
 (d) a light chain of SEQ ID NO:50 and a heavy chain of SEQ ID NO:49; 
 (e) a light chain of SEQ ID NO:52 and a heavy chain of SEQ ID NO:51 and, 
 (f) a light chain of SEQ ID NO:54 and a heavy chain of SEQ ID NO:53. 
 
     
     
       3. An antibody, or an antigen-binding portion thereof, that specifically binds human IL-1β, comprising a light chain and a heavy chain, wherein the amino acid sequence of the light chain is given by SEQ ID NO:48 and the amino acid sequence of the heavy chain is given by SEQ ID NO:68. 
     
     
       4. A pharmaceutical composition comprising the antibody or antigen binding portion thereof of  claim 1 . 
     
     
       5. A method of treating rheumatoid arthritis or osteoarthritis, comprising administering to a patient in need thereof an effective amount of the antibody or antigen binding portion thereof, of  claim 1 . 
     
     
       6. A pharmaceutical composition comprising the antibody or antigen binding portion thereof of  claim 2 . 
     
     
       7. A method of treating rheumatoid arthritis or osteoarthritis, comprising administering to a patient in need thereof an effective amount of the antibody or antigen binding portion thereof, of  claim 2 .